Free Journal of - Exploring the binding mechanism of phosphoramidate derivative with DNA: Spectroscopy, calorimetry and modeling



Exploring the  binding mechanism of phosphoramidate derivative with DNA: Spectroscopy, calorimetry and  modeling
Gongke Wang a, Hongwei Wu b, Dongchao Wang a, Changling Yan a, Yan Lu a,⇑





  1. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, PR China
  2. Department of Chemistry, School of Basic  Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China
h i g h l i g h t s

" Medically important phosphoramidate derivative HMPAP is synthesized.
" HMPAP  is intercalative binding into ctDNA  helix.
" Hydrogen bonding may play an essential role in  the binding of HMPAP  with ctDNA.
" This  binding interaction is
predominantly enthalpy driven.

a r t i c l e    i  n f o

  • Article history:
  • Received 29 June 2012
  • Received in revised form 11 November 2012
  • Accepted 16 November 2012
  • Available online 5 December 2012

a b s t r a c t  

In this study, one of the amino phosphine ester derivatives a-(3-hydroxy-4-methoxyphenyl)-N-phenyl- a-aminophosphonate (HMPAP)  was synthesized, and the molecular interaction of HMPAP  with ct-DNA has been investigated by UV–Vis  absorption spectra, fluorescence spectra, isothermal titration calorime-try (ITC) and molecular modeling. The  binding constant (Kb) of HMPAP  to ct-DNA at different tempera- tures were calculated from fluorescence spectra. According to the UV–Vis  absorption spectra, ethidium bromide displacement studies and ITC experimental results, we  can  conclude that HMPAP is an  interca- lator. The molecular modeling results indicated that HMPAP can  slide into the G–C rich region of ct-DNA. ITC data showed that ct-DNA/HMPAP binding  is enthalpy controlled. Furthermore, the results obtained from molecular modeling corroborated the experimental results obtanied from spectroscopic and ITC investigations.

  2012 Elsevier B.V. All rights reserved.

Keywords:
Amino phosphine ester derivative
DNA Intercalation Spectroscopy
Isothermal titration calorimetry
Molecular modeling

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